Selumetinib (AZD6244)

457, 68

HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation

AZD6244 is current in Phase II clinical trial against non-small-cell lung carcinoma (NSCLC).

50 or 100mg/kg

14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1]

AZD6244 significantly inhibits phosphorylation of ERK1/2 in 2-1318, 5-1318, 26-1004 and 4-1318 xenografts and induces apoptosis in primary 2-1318 cells by activating the caspase pathway. [1] AZD6244 could inhibit the tumor growth in HT-29 xenograft, which is a colorectal tumor model carrying a B-Raf mutation, at a dose of 100 mg/kg and the tumor growth inhibition of AZD6244 is better than it of Gemcitabine. [3] Otherwise AZD6244 could inhibit HCC xenografts tumor growth, which associated with increased apoptosis and down-regulation of cell cycle regulators, including cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc. [4]

Assay of MEK Kinase Activity, Anti-MEK1 antibody is used to immunoprecipitate MEK1 molecules. MEK kinase activity is measured as the ability of immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay using MBP as the end point of the assay. Phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum-dried before exposure to X-ray film.

DMSO 92 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide